As a result of my career-long research on the impact of low IL-2 production in SLE, I have been an advocate for the further exploration and clinical development of low-dose IL-2 as a potential treatment strategy in this patient population. Our group generated data demonstrating the importance of IL-2 in mice with lupus, which piqued the interest of other investigators in the field. We had seen that IL-2–deficient mice develop severe autoimmunity marked by reduced Treg numbers and the systemic expansion of pathogenic T-cell effectors, which suggested that IL-2 is crucial for the maintenance of T-cell–mediated self-tolerance. Our data also suggested that the administration of IL-2 to lupus-prone mice protects against end-organ damage and suppresses inflammation by dually limiting IL-17–producing CD3+CD4-CD8- (double-negative) T cells and expanding Treg.

Low-dose IL-2 is an investigational treatment approach in SLE that has shown promise in preclinical and early clinical studies. Since IL-2 is upstream from several pathways, the administration of low-dose IL-2 allows for the following to occur: (1) the correction of Tregs; (2) the suppression of T helper 17 cell production; (3) the suppression of CD41+ T cells and T follicular helper cells; and (4) the enhancement of cytotoxic responses, which is needed in patients with SLE. In fact, the lack of IL-2 production by the CD41+ T cells of patients with SLE may account for the loss of CD25 expression in Tregs, which could be selectively reversed by stimulation with low doses of IL-2. 

While there is plenty of reason for optimism based on preclinical data, the clinical data have been relatively limited thus far. There is a placebo-controlled, single-center trial conducted by He et al in which 60 patients with active SLE had rapid and significant disease improvement at week 24 with low-dose IL-2 therapy compared with placebo (Systemic Lupus Erythematosus Responder Index 4 response, 66% vs 37%). Total cumulative corticosteroid doses were also reduced more during treatment with low-dose IL-2 than with placebo. With minimal side effects and the opportunity to limit the total cumulative corticosteroid dose, I am optimistic that low-dose IL-2 will become a beneficial supplement in SLE management, but further study is required.